EP0387757A2 - Utilisation des 5'-déoxy-5'-méthylthioadénosine, s-adénosylméthionine et leurs sels pour la préparation de compositions pharmaceutiques favorisant la repousse des cheveux chez des sujets atteints de calvitie - Google Patents
Utilisation des 5'-déoxy-5'-méthylthioadénosine, s-adénosylméthionine et leurs sels pour la préparation de compositions pharmaceutiques favorisant la repousse des cheveux chez des sujets atteints de calvitie Download PDFInfo
- Publication number
- EP0387757A2 EP0387757A2 EP90104641A EP90104641A EP0387757A2 EP 0387757 A2 EP0387757 A2 EP 0387757A2 EP 90104641 A EP90104641 A EP 90104641A EP 90104641 A EP90104641 A EP 90104641A EP 0387757 A2 EP0387757 A2 EP 0387757A2
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- EP
- European Patent Office
- Prior art keywords
- mta
- pharmaceutical compositions
- same
- deoxy
- hair growth
- Prior art date
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Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
- A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
- A61K31/7076—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines containing purines, e.g. adenosine, adenylic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/60—Sugars; Derivatives thereof
- A61K8/606—Nucleosides; Nucleotides; Nucleic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q7/00—Preparations for affecting hair growth
Definitions
- This invention relates to the use of 5'-deoxy-5′-methylthio-adenosine (MTA), S-adenosylmethionine (SAMe) and their pharmaceutically acceptable salts in the preparation of pharmaceutical compositions favouring hair growth in subjects suffering from baldness, and to the relative pharmaceutical compositions.
- MTA 5'-deoxy-5′-methylthio-adenosine
- SAMe S-adenosylmethionine
- their pharmaceutically acceptable salts in the preparation of pharmaceutical compositions favouring hair growth in subjects suffering from baldness, and to the relative pharmaceutical compositions.
- Hair does not perform a vital function in man, however it plays a psychological role of primary importance in that the head of hair represents an aesthetic factor, a social factor and a sexual attraction, and its endangering or indeed its loss produces a series of negative and sometimes debilitating psychological effects both in men and women.
- the pilus and the hair follicle form a functionally inseparable unit which during the entire life span undergoes growth cycles in which three consecutive stages can be recognised (Kligman A.M., J. Inv. Derm. 33, 307, 1959. Kligman A.M., Arch. Derm., 83, 175, 1961. Zaun H., Aertzl. Kosmetologie 8, 5, 1978): - an active growth stage (anagen) - an intermediate stage (catagen) - a rest stage (telogen)
- the anagen stage is characterised by intense metabolic activity at the bulb level, leading to the formation of keratin and melanin and to the lengthening of the hair.
- the catagen stage is a transitional stage lasting some weeks.
- the metabolic activity slows down and the bulb, previously adjacent to the deep dermis, slightly retracts towards the epidermis surface.
- the telogen stage corresponds to a period of follicle quiescence.
- the hair growth ceases.
- a permanent physiological renewal takes place which ensures a constant hair density, particularly as the anagen stage is much longer than the telogen stage. Most of the hair, to the extent of about 90% in the case of healthy hair, is therefore in the anagen stage. As about 100,000-150,000 hairs are in the active growth stage in the case of a young adult, it is estimated that 10,000-15,000 hairs are destined to fall out each year, with an average of about 35 hairs per day. Consequently the hair consists of various classes of individual hairs ranging from very fine elements with very short cycles to the thickest having a growth cycle of many years. The differing combination of these groups in varying proportions gives the hair a more or less abundant volume independently of the number of individual hairs present on the scalp.
- Alopecia is characterised by a shortening of the anagen stage; passage to the telogen stage is earlier and the subsequent regrowth results in the formation of increasingly shorter hairs. It is the number of very fine hairs with very short cycles which give hair afflicted with alopecia its poor and sparse appearance. As the telogen stage does not change its duration there is also a relative increase in the proportion of hairs in the telogen stage.
- the object of the present invention is to describe and claim pharmaceutical compositions which substantially improve the trophicity of the scalp and appendages, and more particularly which favour hair growth in subjects suffering from baldness and in particular with androgenetic alopecia, without side effects.
- MTA MTA
- SAMe SAMe
- their pharmaceutically acceptable salts in the preparation of pharmaceutical compositions which favour hair growth in subjects suffering from baldness and in particular with androgenetic alopecia.
- compositions containing MTA, SAMe and their salts of the present invention are active in favouring hair growth in subjects suffering from baldness and in particular in subjects suffering from androgenetic alopecia.
- the patients were divided into two numerically equal groups and treated for 4 months either with MTA orally administered at a dose of 600 mg/day or with a placebo, on the basis of a randomized double blind scheme.
- the response to the treatment was evaluated independently by the doctor and patient in the following manner.
- the patient objectively evaluated the response to treatment with MTA or placebo after 4 months, by choosing one of the following options:
- the experimentors objectively evaluated the response to treatment with MTA or placebo after 4 months on the basis of the following parameters:
- Figure 2 shows graphically the subjective evaluation by the patients relative to hair growth after 4 months of therapy with MTA administered orally or with placebo (p ⁇ 0.05), in terms of the percentage distribution of the 4 hair growth judgement choices as defined above.
- Figure 3 shows graphically the objective evaluation by the experimentors relative to hair growth after 4 months of therapy with MTA administered orally or with placebo (p ⁇ 0.05), in terms of the percentage distribution of the 5 hair growth judgement choices as defined above.
- Figures 2 and 3 show that there is a significant difference in the percentage distribution of the 4 judgement choices available to patients or the 5 judgement choices available to experimentors (chi- square test) between the two groups, ie those treated with MTA and those treated with placebo. In particular, there is a significantly greater frequency of type IV or V judgement given by the experimentors in the group treated with MTA than in the group receiving the placebo.
- the hair growth was evaluated independently by the doctor and patient after 4 months of treatment in the manner described for clinical trial 1.
- Figure 4 shows graphically the subjective evaluation by the patients relative to hair growth after 4 months of therapy with MTA lotion or placebo, in terms of the percentage distribution of the 4 hair growth judgement choices as defined for clinical trial 1.
- Figure 5 shows graphically the objective evaluation by the experimentors relative to hair growth after 4 months of therapy with MTA lotion or placebo in terms of the percentage distribution of the 5 hair growth judgement choices (p ⁇ 0.05) as defined for clinical trial 1.
- a synergic effect was also noted when the therapeutic treatment is effected when alternately using MTA and SAMe with topical, oral and parenteral administration.
- a synergic effect is obtained by treating the patient on alternate days with topically administered MTA and parenterally administered SAMe, or treating the patient with topically administered SAMe and parenterally administered MTA.
- compositions of the present invention whether suitable for systemic or topical administration, have proved to be able to significantly favour hair growth in subjects suffering from baldness and in particular subjects suffering from androgenetic alopecia. It should also be noted that the pharmaceutical compositions prepared from the active principles of the present invention do not induce any negative side effect and are practically free of toxicity at therapeutic doses for any method of administration.
- compositions prepared from MTA, SAMe and their pharmaceutically acceptable salts according to the present invention and suitable for systemic, oral or parenteral administration can contain a quantity of active principle, whether MTA or SAMe, of between 50 and 1600 mg, and preferably of between 600 and 1200 mg
- compositions of the present invention suitable for topical administration can contain a quantity of active principle of, in the case of MTA, between 0.1% and 5% by weight, and preferably between 0.25% and 1%, and in the case of SAMe between 0.2% and 16% by weight, and preferably between 2% and 8%, in association with additives and excipients normally used in pharmacy.
- EXAMPLE 1 Tablet containing 50 mg of MTA 1 tablet contains: MTA sulphate (equivalent to 50 mg MTA) 58.2 mg Microcrystalline cellulose 37.8 mg Pregelatinized starch 151.2 mg Precipitated silica 0.3 mg Magnesium stearate 2.5 mg
- EXAMPLE 2 Tablet containing 100 mg of MTA 1 tablet contains: MTA ascorbate (equivalent to 100 mg MTA) 159.3 mg Microcrystalline cellulose 160.0 mg Lactose 100 mesh 78.2 mg Precipitated silica 0.5 mg Magnesium stearate 2.0 mg
- Controlled-release tablet containing 200 mg of MTA Release time 2 hours 1 tablet contains: MTA citrate (equivalent to 200 mg MTA) 329.3 mg Dibasic calcium phosphate dihydrate 48.2 mg Lactose 100 mesh 100.0 mg Hydroxypropylmethylcellulose 20.0 mg Magnesium
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Molecular Biology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Dermatology (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Biochemistry (AREA)
- Engineering & Computer Science (AREA)
- Birds (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Cosmetics (AREA)
- Saccharide Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT8919747A IT1229479B (it) | 1989-03-13 | 1989-03-13 | Impiego di 5' deossi 5' metiltioadenosina, di s adenosilmetionina e dei loro sali per la preparazione di composizioni farmaceutiche atte a favorire la crescita dei capelli in soggetti affetti da calvizie e composizioni farmaceutiche relative. |
| IT1974789 | 1989-03-13 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| EP0387757A2 true EP0387757A2 (fr) | 1990-09-19 |
| EP0387757A3 EP0387757A3 (en) | 1990-12-12 |
| EP0387757B1 EP0387757B1 (fr) | 1993-12-15 |
Family
ID=11160891
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP90104641A Expired - Lifetime EP0387757B1 (fr) | 1989-03-13 | 1990-03-12 | Utilisation des 5'-déoxy-5'-méthylthioadénosine, s-adénosylméthionine et leurs sels pour la préparation de compositions pharmaceutiques favorisant la repousse des cheveux chez des sujets atteints de calvitie |
Country Status (12)
| Country | Link |
|---|---|
| EP (1) | EP0387757B1 (fr) |
| JP (1) | JPH0778012B2 (fr) |
| KR (1) | KR900013935A (fr) |
| AT (1) | ATE98467T1 (fr) |
| AU (1) | AU637999B2 (fr) |
| CA (1) | CA2012045C (fr) |
| DE (1) | DE69005160T2 (fr) |
| DK (1) | DK0387757T3 (fr) |
| ES (1) | ES2062138T3 (fr) |
| IT (1) | IT1229479B (fr) |
| PH (1) | PH30798A (fr) |
| ZA (1) | ZA901930B (fr) |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0540854A3 (en) * | 1991-09-10 | 1993-07-28 | Sansho Seiyaku Co., Ltd. | Preparation for promoting hair growth |
| US5656264A (en) * | 1991-09-10 | 1997-08-12 | Sansyo Seiyaku Co., Ltd. | Method for promoting hair growth |
| WO2000047172A1 (fr) * | 1999-02-10 | 2000-08-17 | Taisho Pharmaceutical Co., Ltd. | Agent de stimulation de la croissance capillaire et recherche systematique de substances ayant cet effet |
| WO2003053412A1 (fr) * | 2001-12-12 | 2003-07-03 | Chemistry & Health International B.V. | Granules stables contenant de la s-adenosylmethionne et leur procede de preparation |
| WO2005044205A1 (fr) * | 2003-11-11 | 2005-05-19 | Shiseido Company, Ltd. | Procede et composition destines a epaissir les cheveux |
| WO2005058273A1 (fr) * | 2003-12-05 | 2005-06-30 | Apr Applied Pharma Research Sa | Compositions contenant de la methylthioadenosine (mta) et utilisation topique de ces compositions |
| US7423065B2 (en) | 1997-10-02 | 2008-09-09 | Board Of Trustees Of Southern Illinois University | Therapeutic use of methionine-derivitives to reduce the toxicity of noise |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IT1247903B (it) * | 1991-02-25 | 1995-01-05 | Bioresearch Spa | Impiego della s-adenosil-l-metionina nel trattamento della colestasi intraepatica da nutrizione parenterale totale |
| KR100616342B1 (ko) * | 1998-10-26 | 2006-08-29 | 가부시키가이샤 시세이도 | 양모 조성물 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2313937A1 (fr) * | 1975-06-09 | 1977-01-07 | Anvar | Medicament a base de 5' thioethers de l'adenosine |
| IT1169772B (it) * | 1983-08-24 | 1987-06-03 | Bioresearch Spa | Composizioni terapeutiche per uso orale contenenti sali stabili della s-adenosil-l-metionina |
| IT1169774B (it) * | 1983-08-24 | 1987-06-03 | Bioresearch Spa | Composizioni terapeutiche iniettabili contenenti sali stabili della s-adenosil-l-metionina |
| NL8302984A (nl) * | 1983-08-26 | 1985-03-18 | Philips Nv | Beeldweergeefinrichting met een ruisdetektor. |
-
1989
- 1989-03-13 IT IT8919747A patent/IT1229479B/it active
-
1990
- 1990-03-12 ES ES90104641T patent/ES2062138T3/es not_active Expired - Lifetime
- 1990-03-12 DK DK90104641.7T patent/DK0387757T3/da active
- 1990-03-12 AT AT90104641T patent/ATE98467T1/de not_active IP Right Cessation
- 1990-03-12 EP EP90104641A patent/EP0387757B1/fr not_active Expired - Lifetime
- 1990-03-12 DE DE90104641T patent/DE69005160T2/de not_active Expired - Lifetime
- 1990-03-13 ZA ZA901930A patent/ZA901930B/xx unknown
- 1990-03-13 KR KR1019900003302A patent/KR900013935A/ko not_active Ceased
- 1990-03-13 CA CA002012045A patent/CA2012045C/fr not_active Expired - Fee Related
- 1990-03-13 JP JP2060127A patent/JPH0778012B2/ja not_active Expired - Fee Related
- 1990-03-13 AU AU51273/90A patent/AU637999B2/en not_active Ceased
- 1990-03-13 PH PH40185A patent/PH30798A/en unknown
Cited By (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0540854A3 (en) * | 1991-09-10 | 1993-07-28 | Sansho Seiyaku Co., Ltd. | Preparation for promoting hair growth |
| US5656264A (en) * | 1991-09-10 | 1997-08-12 | Sansyo Seiyaku Co., Ltd. | Method for promoting hair growth |
| US7557142B2 (en) | 1996-10-03 | 2009-07-07 | Board Of Trustees Of Southern Illinois University | Therapeutic use of methionine to reduce the toxicity of platinum-containing anti-tumor compounds |
| US7423065B2 (en) | 1997-10-02 | 2008-09-09 | Board Of Trustees Of Southern Illinois University | Therapeutic use of methionine-derivitives to reduce the toxicity of noise |
| WO2000047172A1 (fr) * | 1999-02-10 | 2000-08-17 | Taisho Pharmaceutical Co., Ltd. | Agent de stimulation de la croissance capillaire et recherche systematique de substances ayant cet effet |
| WO2003053412A1 (fr) * | 2001-12-12 | 2003-07-03 | Chemistry & Health International B.V. | Granules stables contenant de la s-adenosylmethionne et leur procede de preparation |
| EP1325740A1 (fr) * | 2001-12-12 | 2003-07-09 | Chemistry & Health International B.V. | Granules stables contenant de la s-adenosylmethionine et procede de preparation |
| US7048948B2 (en) | 2001-12-12 | 2006-05-23 | Chemistry & Health Int Bv | Stable granulates containing S-adenosylmethionine and process for the preparation thereof |
| WO2005044205A1 (fr) * | 2003-11-11 | 2005-05-19 | Shiseido Company, Ltd. | Procede et composition destines a epaissir les cheveux |
| JPWO2005044205A1 (ja) * | 2003-11-11 | 2007-05-17 | 株式会社資生堂 | 毛髪の太毛化の方法及び組成物 |
| WO2005058273A1 (fr) * | 2003-12-05 | 2005-06-30 | Apr Applied Pharma Research Sa | Compositions contenant de la methylthioadenosine (mta) et utilisation topique de ces compositions |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH0363225A (ja) | 1991-03-19 |
| PH30798A (en) | 1998-10-17 |
| ATE98467T1 (de) | 1994-01-15 |
| IT8919747A0 (it) | 1989-03-13 |
| EP0387757A3 (en) | 1990-12-12 |
| DE69005160D1 (de) | 1994-01-27 |
| AU5127390A (en) | 1990-11-01 |
| EP0387757B1 (fr) | 1993-12-15 |
| DE69005160T2 (de) | 1994-03-31 |
| ZA901930B (en) | 1990-12-28 |
| CA2012045C (fr) | 2001-02-13 |
| CA2012045A1 (fr) | 1990-09-13 |
| JPH0778012B2 (ja) | 1995-08-23 |
| IT1229479B (it) | 1991-09-03 |
| ES2062138T3 (es) | 1994-12-16 |
| DK0387757T3 (da) | 1994-03-21 |
| KR900013935A (ko) | 1990-10-22 |
| AU637999B2 (en) | 1993-06-17 |
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